Ultraporous sol gel monoliths

ABSTRACT

Ultraporous sol gel monoliths and methods for preparing the same are provided, having superior flow characteristics for chromatography and analytical chemistry applications. The methods for forming an ultra porous sol-gel monolith include (a) forming a solution comprising a porogen, a matrix dissolving catalyst and a sol gel precursor; (b) allowing the solution to form a gel; and (c) drying the gel at an elevated temperature. The ultraporous sol gel monoliths are characterized by a porosity of up to about 97%, a BET surface area of at least about 50 m 2 /g and substantially no micropores.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application is a Divisional of U.S. patent application Ser.No. 11/018,168, filed Dec. 20, 2004.

FIELD OF THE INVENTION

This invention relates generally to sorbents useful in analyticalapplications and methods of preparing and using them.

BACKGROUND OF THE INVENTION

A typical sol-gel process involves the transition of a liquid colloidalsolution “sol” phase into a solid porous “gel” phase, followed by dryingand sintering the resulting gel monolith at elevated temperatures. Theconventional sol-gel process for the formation of ceramic or glassmaterials consists of hydrolysis of a metal alkoxide precursor,typically tetramethylorthosilicate or tetraethylorthosilicate forforming silica, in the presence of an acid or base catalyst. Thereaction mixture is placed in a desired receptacle and undergoeshydrolysis and polymerization, resulting in a wet porous gel monolith ormatrix formed in situ. After drying the wet gel monolith in a controlledenvironment to remove the fluid from the pores, the dry gel monolith canbe calcined into a solid glass-phase monolith. The materials produced bythis process display connected open pores with a generally narrow rangeof the pore size distribution. This type of air-dried xerogel typicallypossesses numerous pores or channels well below 15 Å in diameter,depending on the synthesis conditions.

In the use of these porous materials as support or separation devices,the average size and size distribution of pores should be preciselycontrolled so as to optimize the function of supported substances or theseparation efficiency. For many applications the porous material shouldcontain a defined mesopore size distribution in addition to the networkof macropores present. To that end, many investigators have attempted tocontrol the size and distribution of macropores by adjusting thereaction parameters of gel preparation, including adding pore formingagents during gel preparation, or remodeling the interior surface toenlarge and/or provide a more uniform size distribution of mesopores.

For example, the influence of the catalyst concentration on the poresizes of the resultant gel monoliths is illustrated by U.S. Pat. No.5,264,197 to Wang, which describes preparing a sol gel monolithicmaterial by adjusting the relative concentrations of an alcohol and/orcatalysts such as HCl or HF at concentrations up to a maximum of about0.05 moles per mole of tetraethoxysilane. This patent describes thatwhen the alcohol is ethanol and the catalysts are hydrofluoric acid andhydrochloric acid, the average pore radii in the dry gel can be tailoredto selected values in the range of 10 Å to 100 Å by controlling therelative concentrations of the ethanol and the catalyst.Correspondingly, the gel surface area is reported to be tailored tovalues in the range of 600 to 1100 m²/g. However, the process does notproduce enough macropores which are generally required forchromatographic separations.

U.S. Patent Application Publication Nos. 2003/0068266 and 2003/0069122describe that the use of HF can promote the formation of larger poresizes, thus reducing the tendency for cracking of gel monoliths.However, the inventors point out that the use of catalysts such as HFalso shortens gelation times, and can result in insufficient time forprocessing, or for bubbles to diffuse out of the gel, thereby degradingthe quality of the gel produced. A method of manufacturing a xerogelmonolith is described that includes preparing a first solutioncomprising metal alkoxide, a second solution comprising a catalyst, andmixing the first and second solutions together, where at least one ofthe solutions is cooled to achieve a mixture temperature for the thirdsolution which is substantially below room temperature. In so doing, themixture reportedly has a significantly longer gelation time at themixture temperature as compared to a room temperature.

Another approach is described in U.S. Pat. No. 5,624,875 to Nakanishi,which describes the solidification of the solution to form a sol gel,the aging of the gel for an appropriate period, and then the immersionof the gel in a matrix dissolving agent, such as sodium hydroxide,aqueous ammonia, or hydrofluoric acid. This patent states that duringthe immersion process, substitution of external solution with thesolvent-rich phase takes place, allowing contact of the externalsolution with the inner-surface of silica-rich phase, and that when theexternal solution can dissolve the matrix, the inner wall is subjectedto a dissolution and re-precipitation process, resulting in the loss ofsmaller pores and the increase of larger pores. This patent states thatthis step is essential for creating sharply distributed mesopores. Thus,this patent demonstrates that the sol gel must first be formed and thenimmersed in a matrix dissolving agent in order to obtain the desiredmesopore distribution, a time consuming and difficult to control step.

Similarly, U.S. Pat. No. 6,207,098 to Nakanishi reports a process forproducing inorganic porous materials composed of glass or glass ceramiccomponents reportedly having interconnected continuous macropores with amedian diameter larger than 0.1 μm and mesopores in the walls of saidmacropores having a median diameter between 2 and 100 nm. The processreportedly includes (a) dissolving a water-soluble polymer or other poreforming agent and a precursor for a matrix dissolving agent in a mediumthat promotes the hydrolysis of an organometallic compound; (b) mixingwith an organometallic compound which contains hydrolyzable ligands; (c)solidifying the mixture through the sol-gel transition, whereby a gel isprepared which has three dimensional interconnected phase domains onerich in solvent the other rich in inorganic component in which surfacepores are contained; (d) setting the matrix dissolving agent free fromits precursor, whereby the matrix dissolving agent modifies thestructure of said inorganic component; (e) removing the solution byevaporation drying and/or heat-treatment; (f) calcining the gel to formthe porous material. However, it is very difficult to eliminatemicropores using this process, limiting the performance duringchromatographic separations. Further, this process requires preparing agel and then performing an additional step to modify the structure ofthe gel, which is a complicated and time consuming procedure.

U.S. Pat. Nos. 6,562,744 and 6,531,060 to Nakanishi further describeinorganic porous materials contained in a confined space having at leastone dimension less than 1 mm across and in liquid tight contact with thewalls of the container, such as a capillary. The process involvesthermally decomposing a component that modifies the gel structure, suchas an amide compound that is capable of making the reaction system basicwhen the compound is thermolysed.

U.S. Pat. No. 6,398,962 to Cabrera further describes using the method ofNakanishi for preparation of a monolithic sorbent for use in simulatedmoving bed chromatography. The monolithic sorbent is reportedly based onshaped SiO₂ bodies having macropores of diameter from 2 to 20 μm andmesopores of diameter from 2 to 100 nm. However, as described above, theprocess for preparing the monoliths is laborious and time consuming.

U.S. Patent Application Publication No. 2003/0150811 describes a porousinorganic/organic hybrid material and a process for forming the samewherein the pores of diameter less than about 34 Å reportedly contributeless than 110 m²/g to less than 50 m²/g to the specific surface area ofthe material. The process reportedly involves forming porousinorganic/organic hybrid particles, modifying the pore structure of theporous hybrid particles, and coalescing the porous hybrid particles toform a monolith material. This application also reports the hydrothermaltreatment of hybrid monolithic silica, formed in a similar process asdescribed in the above patents, in order to modify the pore structure.However, these processes are laborious and time consuming, and may noteliminate micropores.

U.S. Patent Application Publication No. 2001/0033931 assigned to Watersdescribes porous inorganic/organic hybrid particles reportedly having achromatographically-enhancing pore geometry. The process for preparingthe porous particles reportedly involves the three step process offorming the particles, suspending the particles in an aqueous medium insurfactant and gelling the particles into porous spherical particles ofhybrid silica using a base catalyst, and modifying the pore structure byhydrothermal treatment. The process is thus laborious and timeconsuming.

Sol gel monoliths are also subject to cracking and shrinking during thedrying step of the fabrication process. Approaches to reduce thecracking have been attempted, focused on increasing the pore sizes ofthe gel monolith to reduce the capillary stresses generated duringdrying. For example, U.S. Pat. No. 5,023,208 to Pope describessubjecting the gel to a hydrothermal aging treatment, which reportedlycauses silica particles to migrate and fill small pores in the porousgel matrix, and increase the average pore size. U.S. Pat. No. 6,210,570to Holloway describes that “syneresis,” or the shrinkage in volume as ahydrosol progresses to a hydrogel, can occur to the extent that a volumeof a material can decrease by a factor of 100. U.S. Pat. No. 6,620,368to Wang describes that the density of the gel at the end of the firststage of liquid removal process corresponds to a shrinkage in the lineardimension of between about 15% and 35%.

U.S. Pat. No. 6,528,167 to O'Gara describes a method of preparingchromatographic particles for performing separations or forparticipating in chemical reactions, including: (a) prepolymerizing amixture of an organoalkoxysilane and a tetraalkoxysilane in the presenceof an acid catalyst to produce a polyalkoxysiloxane; (b) preparing anaqueous suspension of the polyalkoxy siloxane further comprising asurfactant, and gelling in the presence of a base catalyst so as toproduce porous particles having silicon C₁₋₇ alkyl groups, substitutedor unsubstituted aryl groups, substituted or unsubstituted C₁₋₇,alkylene, alkenylene, alkynylene, or arylene groups; (c) modifying thepore structure of the porous particles by hydrothermal treatment; and(d) replacing one or more surface C₁₋₇ alkyl groups, substituted orunsubstituted aryl groups, substituted or unsubstituted C₁₋₇ alkylene,alkenylene, alkynylene, or arylene groups of the particle with hydroxyl,fluorine, alkoxy, aryloxy, or substituted siloxane groups. The replacingstep involves reacting the hybrid particle with aqueous H₂O₂, KF, andKHCO₃ in an organic solution, which may further include a porogen.

U.S. Pat. No. 6,346,140 to Miyazawa describes a process for preparing aporous solid for gas adsorption separations wherein the micropore volumeis at least 10% and preferably from 20% to 50% of the total pore volume.This patent also describes porous solids having total micropore volumesof at least 0.05 cc/g, and mesopore volumes of 0.25 to 0.58 cc/g. Inaddition, this patent teaches the importance of limiting the surfactantbelow a concentration of 29 μl in order to allow formation ofmicropores. Thus this patent teaches the production of a sol gel havingsignificant micropores.

Thus, numerous processes for preparing sol gel monolithic sorbents areknown in the art of chromatographic separations. However, production ofsorbents having the desired distribution of macro- and mesopores withsubstantially no micropores remains an unsolved problem. In addition,the procedures known in the art are complicated and difficult tocontrol, costly and time consuming. Therefore, there is a need in theart for methods of producing ultraporous sol gel monolithic sorbentsproviding superior flow characteristics and having the desireddistribution of macro- and mesopores with substantially no micropores.In addition, there is a need in the art for procedures that are simpleand uncomplicated, provide good control over the reaction and theproducts, and that are less costly and time consuming to produce and touse.

SUMMARY OF THE INVENTION

Accordingly, it is a primary object of the invention to address theaforementioned need in the art by providing an ultraporous sol gelmonolith providing superior porosity and mobile phase flowcharacteristics.

It is another object of the invention to provide an ultraporous sol gelmonolith having a desired macropore volume.

It is yet another object of the invention to provide an ultraporous solgel monolith having a desired mesopore surface area and volume.

It is a further object of the invention to provide an ultraporous solgel monolith having substantially no micropores.

Accordingly, there is provided an ultraporous sol gel monolith, whereinthe sol gel monolith is characterized by having a porosity of up toabout 97%. Preferably, the porosity of the sol gel monolith is at leastabout 60%. In particular embodiments, the ultraporous sol gel monolithis characterized by a porosity of from about 85% to about 97%. Theultraporous sol gel monolith provides superior porosity while havingsubstantially no micropores.

The ultraporous sol gel monolith is characterized by a total pore volumesufficient to provide a porous monolith, preferably at least about 1.0cc/g, more preferably at least about 2.0 cc/g. In particularembodiments, the ultraporous sol gel monolith is characterized by atotal pore volume of from about 4.0 cc/g to about 7.0 cc/g.

The ultraporous sol gel monolith is characterized by a BET surface areafrom at least about 50 m²/g and more preferably at least about 100 m²/g.In particular embodiments, the BET surface area is from about 200 m²/gto about 700 m²/g.

The ultraporous sol gel monolith is formed from a sol gel precursor,typically a metal or metalloid compound having hydroxyl or hydrolyzableligands and that are capable of undergoing a sol gel reaction to form asol gel. Suitable hydrolyzable ligands include, but not limit to,halogen, alkoxy, amino or acyloxy. The metal or metalloid compoundpreferably comprises Si, and in some embodiments, can include Ge, Sn,Al, Ga, Mg, Mb, Co, Ni, Ga, Be, Y, La, Pb, V, Nb, Ti, Zr, Ta, W, Hf, orcombinations thereof. In certain preferred embodiments, the sol gelprecursor is an alkoxide and/or halide of silicon, germanium, aluminum,titanium, zirconium, vanadium, or hafnium, or mixtures thereof.

The ultraporous sol gel monolith can be further modified, such that thesurface of the sol gel monolith is modified with polar or nonpolarmoieties to provide particular adsorption characteristics when used as asorbent or catalyst, for example. In particular embodiments, the surfacecan be modified with a silane having the formula

R¹ _(n)—Si—X_(4-n),

wherein R¹ is independently selected from hydrogen, C₁-C₁₀₀ substitutedor unsubstituted hydrocarbyl, cycloalkyl, heterocycloalkyl, aryl, orheteroaryl; wherein the substituents are selected from C₁-C₁₂hydrocarbyl, hydroxyl, alkoxy, halogen, amino, nitro, sulfo, cyano,glycidyl, carbamido, and carbonyl, wherein n is 0, 1, 2, or 3, and X isa leaving group. The sol gel monolith can also be modified with anendcapping reagent, such as trimethylchlorosilane.

The invention further provides a method for forming an ultra poroussol-gel monolith, comprising (a) forming a solution comprising aporogen, a catalyst and a sol gel precursor; (b) allowing the solutionto form a gel; and (c) drying the gel at an elevated temperature. Thesolution of step (a) can be aqueous, or a mixture of organic solventsand water. Preferably, the organic solvent is a water miscible solvent,such as an alkanol, formamide. More preferably, the water misciblesolvent is a straight chain or branched alkanol, such as an alkanolhaving the formula CH₃(CH₂)_(n)OH, wherein n is from 0-12. Ethanol,isopropanol, and methanol are preferred solvents, and can be used aloneor as mixtures.

The catalyst is a matrix dissolving agent, and can further compriseadditional catalysts such as HCl or nitric acid. Preferably the matrixdissolving agent is hydrofluoric acid at a concentration of up to 1.0mole per mole of the sol-gel precursor. The hydrofluoric acid can alsobe provided by a hydrofluoric acid source. Hydrofluoric acid sourcesinclude fluorinated and/or fluoride containing compounds that cangenerate HF through hydrolysis or dissociation in the solution of step(a), before or during the gelation process. In particular embodiments,hydrofluoric acid sources include, without limitation, F₂(g), fluoridesof Group I elements, such as KHF₂; fluorides of Group II elements;fluorides of Group III elements such as BF₃; fluorides of Group IVelements such as SiF₄, GeF₄, and fluorosilanes (e.g., SiFH₃,fluorotriethoxysilane, fluorodichloroethoxysilane), fluorogermanes(e.g., GeFH₃, fluorotriethoxygermane); fluorides of group V elementssuch as NF₃, PF₃, PF₅, PF₃Cl₂; fluorides of Group VI elements such asSF₄, SF₆, as well as fluoride salts such as NH₄HF₂, or mixtures thereof.A preferred hydrofluoric acid source is a fluorosilane such asfluorotriethoxysilane. Thus, in certain embodiments, the sol gelprecursor can also function to provide some or all of the matrixdissolving agent.

Sol gel precursors include metal or metalloid compounds having hydroxylor hydrolyzable ligands that are capable of undergoing a sol gelreaction to form a sol gel. Typical metals include silicon, germanium,aluminum, titanium, zirconium, vanadium, niobium, tantalum, tungsten,tin, or hafnium, or mixtures thereof, having reactive metal oxides,halides, amines, etc., capable of reacting to form a sol gel. Additionalmetal atoms that can be incorporated into the sol gel precursors includemagnesium, molybdenum, cobalt, nickel, gallium, beryllium, yttrium,lanthanum, tin, lead, and boron, without limitation.

In particular embodiments, the sol gel precursor can further comprise anorganic substituent, and can include an organosilane, for example, suchas an alkoxy-, halo-, acyloxy- or amino silane, further comprising anorganic substituent, such as a saturated or unsaturated hydrocarbylsubstituent, aryl substituent, or mixtures thereof. Typicalalkoxysilanes can include, for example, alkyltrialkoxysilane,cycloalkyltrialkoxysilane, dialkyldialkoxysilane, trialkylalkoxysilane,tetraalkoxysilane, vinyltrialkoxysilane, allyltrialkoxysilane,phenylalkyldialkoxysilane, diphenylalkoxysilane, ornaphthyltrialkoxysilane, or mixtures thereof. The sol gel precursorcomprising an organic substituent can also include other organometalliccompounds such as organogermanes, or organosubstituted titanium,aluminum, zirconium or vanadium alkoxides, and the like. In anotherpreferred embodiment, the silane is a mixture of silanes comprising atrialkoxysilane and a tetraalkoxysilane.

The porogen can be a hydrophilic polymer or a surfactant. Suitablehydrophilic polymers include, for example, polyethyleneglycol, sodiumpolystyrene sulfonate, polyacrylate, polyallylamine, polyethyleneimine,polyethylene oxide, polyvinylpyrrolidone, polymers of amino acids,polysaccharides such as cellulose ethers or esters, such as celluloseacetate, or the like. A preferred hydrophilic polymer ispolyethyleneglycol. The molecular weight is not limited to anyparticular, range and generally can have a molecular weight up to about1,000,000 g/mole.

The porogen can also be a surfactant, such as a nonionic surfactant, anionic surfactant, an amphiphilic surfactant, or mixtures thereof. In thepractice of the inventive methods, step (a) and (b) can be performed ata temperature between the freezing point and boiling point of thesolution, more typically at a temperature of from about 0° C. to about60° C. In other aspects of the invention, step (b) comprises allowingthe solution to form a gel in situ or transferring at least a portion ofthe solution to a receptacle and allowing the solution to form a gel inthe receptacle. Any shape or form of receptacle is suitable, withoutlimitation. For example, the receptacle can be a capillary tubing (e.g.,comprising fused silica, borosilicate glass, doped silicate or glass), amold, a column, a chip, a microfluidics platform, a plate, or anintegrated analytical and detection system, e.g., including massspectrometric detection. Suitable sizes for capillary tubing includediameters of between about 10 μm and about 1000 μm, or more typicallybetween about 100 μm and about 530 μm.

In the practice of the inventive methods, step (c) can be performed at atemperature up to about 400° C. In preferred methods, the temperature isfrom about 100° to about 200° C., and in other preferred methods, thetemperature is from about 200° to about 400° C.

The method for preparing an ultraporous sol gel monolith can furthercomprise step (d) calcining the gel at a temperature of at least 400° C.Preferably, the gel is calcined at a temperature of from about 400° C.up to about 1000° C. In particular embodiments, the drying and calciningsteps are performed at the same time, by, for example, heating the solgel to dryness at 200° C. and then increasing the temperature to 400° C.or more. In addition, the drying and calcining steps can be performedtogether by gradually raising the temperature from below about 400° C.to a higher temperature in the range of 400° C. to about 1000° C., oreven greater. Furthermore, the ultraporous sol gel monolith can besolidified into a porous glass monolith, which is also useful forchromatographic separation or other purposes, and can include furthermodifying its pore surfaces, for example, using polymeric, organic orinorganic phases and/or layers that can be bonded and/or coated ontoporous glass monolith pore surfaces.

The methods for forming an ultraporous sol gel monolith can be used toprepare a sol gel monolith characterized by a porosity of up to about97%, a preferred total pore volume of at least about 1.0 cc/g. Inparticular embodiments, the ultraporous sol gel monolith ischaracterized by a porosity of from about 85% to about 97% and a totalpore volume of from about 4.0 cc/g to 7.0 cc/g. Such an ultraporous solgel monolith provides a superior chromatography sorbent having a reducedbackpressure at chromatographically useful flow rates.

The invention further comprises methods for separating a mixture ofanalytes, comprising applying the mixture of analytes to the ultraporoussol gel monolith, and eluting the analytes using a mobile phase. Themonoliths thus prepared are versatile and suitable for separationsutilizing thin layer chromatography, high performance liquidchromatography, reversed phase chromatography, normal phasechromatography, ion chromatography, ion pair chromatography, reversephase ion pair chromatography, ion exchange chromatography, affinitychromatography, hydrophobic interaction chromatography, size exclusionchromatography, chiral recognition chromatography, perfusionchromatography, electrochromatography, partition chromatography,microcolumn liquid chromatography, capillary chromatography, capillaryzone electrophoresis (CZE), nano-LC, open tubular liquid chromatography(OTLC), capillary electrochromatography (CEC), liquid-solidchromatography, preparative chromatography, hydrophilic interactionchromatography, supercritical fluid chromatography, precipitation liquidchromatography, bonded phase chromatography, fast liquid chromatography,flash chromatography, liquid chromatography-mass spectrometry, gaschromatography, microfluidics based separations, chip based separationsor solid phase extraction separations, and the like.

Additional objects, advantages and novel features of the invention willbe set forth in part in the description which follows, and in part willbecome apparent to those skilled in the art upon examination of thefollowing, or may be learned by practice of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a scanning electron micrograph of an ultraporous sol gelmonolith.

FIG. 1B shows a scanning electron micrograph showing a cross section ofa capillary column having an internal diameter of 530 μm containing anultraporous sol gel monolith.

FIG. 2 illustrates the t-plot obtained for the ultraporous sol gelmonolith produced by the procedures set forth in Example 2, indicatingsubstantially no micropores.

FIG. 3 illustrates the t-plot obtained for the ultraporous sol gelmonolith produced by the procedures set forth in Example 4, indicatingsubstantially no micropores.

FIG. 4 illustrates the mesopore distribution of the ultraporous sol gelmonolith produced by the procedures set forth in Example 1.

FIG. 5 illustrates the mesopore distribution of the ultraporous sol gelmonolith produced by the procedures set forth in Example 2.

DETAILED DESCRIPTION OF THE INVENTION

I. Definitions and Overview

Before the present invention is described in detail, it is to beunderstood that unless otherwise indicated this invention is not limitedto specific silanes, porogens, or the like, as such may vary. It is alsoto be understood that the terminology used herein is for the purpose ofdescribing particular embodiments only and is not intended to limit thescope of the present invention.

It must be noted that as used herein and in the claims, the singularforms “a,” “and” and “the” include plural referents unless the contextclearly dictates otherwise. Thus, for example, reference to “a porogen”includes two or more porogens; reference to “a silane” includes two ormore silanes, and so forth.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range, and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges, and are also encompassed within the invention, subjectto any specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

As used herein, the term “macropores” refers to pores with diametersgreater than about 0.05 μm (50 nm, or 500 Å); the term “mesopores”refers to pores with diameters between about 2 nm and 50 nm (20 Å-500Å); and the term “micropores” refers to pores with diameters less thanabout 2.0 nm (20 Å).

As used herein, the term “total pore volume” refers to the total volumeof the pores in the monolith, and is usually expressed in cm³/g, orcc/g. The total pore volume can be measured by mercury intrusion, whereHg is pumped into the pores under high pressure.

The term “BET surface area” refers to the determination of surface areausing the BET method, which can be determined using either a singlepoint or multiple point analysis. For example, multipoint nitrogensorption measurements can be made on a Micromeritics TriStar 3000instrument (Norcross, Ga.). The specific surface area can then becalculated using the multipoint BET method, and the mode pore diameteris the most frequent diameter from the log differential pore volumedistribution (dV/d log(D) vs. D). The mesopore volume is calculated asthe single point total pore volume at P/P₀=0.98.

The present inventors have surprisingly discovered that including amatrix dissolving catalyst in the sol gel forming solution throughoutthe gelation process provides ultraporous sol gel monoliths withsuperior flow characteristics for chromatography and analyticalchemistry applications, as well as other applications known in the art.Surprisingly, the sol gels exhibit an ultraporous structure with definedand controlled macropore and mesopore volumes having narrow pore sizedistributions, while virtually eliminating micropores. Such sol gelmonoliths are characterized in having a porosity of up to about 97%,preferably at least about 60% and more preferably, at least about 80%,which provides superior mobile phase flow characteristics, allowing lowback pressure and/or increased flow rates during chromatographicapplications. The ultraporous sol gel monoliths are also characterizedby a total pore volume sufficient to provide a porous monolith,preferably a total pore volume of at least about 1.0 cc/g, and morepreferably at least about 2.0 cc/g. In particular embodiments, the totalpore volume is in the range of about 4.0 to about 7.0 cc/g. Theultraporous sol gel monoliths have BET surface areas of at least 50m²/g, and more preferably, at least about 100 m²/g. In a preferredembodiment, the BET surface area is from about 200 m²/g to about 700m²/g.

In a significant aspect, the ultraporous sol gel monoliths arecharacterized by showing substantially no micropores, as evinced byanalysis of the volume N₂/gram relative to film thickness (or t-plot),as described by Mikail, R., et al. (1968) J. Colloid Interface Sci.26:45. The t-plot analysis shows a y-intercept of zero, indicating thatsubstantially no micropores are present in the sample, within the limitsof measurement using current technology. Thus the term “substantially nomicropores” means that no pore volume due to micropores is measurableusing currently available technologies.

Table 1 presents a summary of representative ultraporous sol gelmonolith pore characteristics obtained using the methods of the presentinvention, as exemplified in the Examples below.

TABLE 1 Ultraporous sol gel monolith pore characteristics Total PoreMesopore Volume BET Surface Area Mesopore Diameter Example Volume (cc/g)(cc/g) (m²/g) (Mode, Å) 1 5.4 1.13 531 102 2 4.6 1.50 290 162 3 5.0 1.34452 142 4 6.9 1.46 526 136 5 6.2 1.36 550 108 6 5.6 1.25 614 104 7 5.21.11 663 85

All of the representative examples in Table 1 exhibited at least about85% porosity. The mesopore volume and mode diameter vary and can becontrolled by reaction conditions, including the amount and type ofporogen, the molecular weight of the porogen, the amount of water, solgelation temperatures, solvent amount and type, and matrix dissolvingcatalyst concentration (e.g., HF or fluorosilanes), as well as the solgel precursor concentration and type. For example, gelation at lowertemperatures results in a sol gel having smaller mesopore diameters.Varying the solvent/water ratio and/or catalyst concentrations alsochanges the pore characteristics that can be obtained. Thus, theexperimental conditions can be fine tuned to obtain particular mesoporeand macropore size distributions and volumes as well as particularporosities.

These data demonstrate the superior and unexpected properties of theultraporous sol gel monoliths of the invention.

II. Methods of Preparing Ultraporous Sol Gel Monoliths

The microstructure of a sol gel monolith is influenced by the rates ofhydrolysis and polymerization which occur during the gelation of the wetgel monolith from the sol. It is known that a silica-based sol can beformed from tetraethylorthosilicate (TEOS, (C₂H₅O)₄Si), for example, bymixing the TEOS with water, a diluent or solvent such as ethyl alcohol,and a catalyst, and hydrolysis occurs with the following reaction:

(C₂H₅O)₄Si+4H₂O→4C₂H₅OH+Si(OH)₄.

The Si(OH)₄ molecules polymerize, resulting in a network of SiO₂ andwater. Numerous factors influence the kinetics of hydrolysis andpolymerization, including the type and concentration of any catalystsand the temperature profile.

The present inventors have surprisingly discovered simple and efficientmethods for forming ultraporous sol-gel monoliths having superiorporosity, and controllable macropore and mesopore volumes and surfaceareas, while virtually eliminating micropores. These monolithicstructures provide superior sorbents for analytical applications. Themethods generally comprise (a) forming a solution comprising a porogen,a catalyst and a sol gel precursor; (b) allowing the solution to form agel; and (c) drying the gel at an elevated temperature.

The solution of step (a) can be aqueous, or a mixture of organicsolvents and water. Preferably, the organic solvent is a water misciblesolvent, such as an alkanol, formamide. More preferably, the watermiscible solvent is a straight chain or branched alkanol, such as analkanol having the formula CH₃(CH₂)_(n)OH, wherein n is from 0-12.Ethanol, isopropanol, and methanol are preferred solvents, and can beused alone or as a mixture.

The catalyst is a matrix dissolving agent, and can further compriseadditional catalysts such as HCl or nitric acid that do not function asmatrix dissolving agents. Preferably the matrix dissolving agent ishydrofluoric acid at a concentration of up to 1.0 mole per mole of thesol-gel precursor. The hydrofluoric acid can also be provided by ahydrofluoric acid source. Hydrofluoric acid sources include fluorinatedand/or fluoride containing compounds that can generate HF throughhydrolysis or dissociation in the solution of step (a), before or duringthe gelation process. In particular embodiments, hydrofluoric acidsources include, without limitation, F₂(g), fluorides of Group Ielements, such as KHF₂; fluorides of Group II elements, fluorides ofGroup III elements, such as BF₃; fluorides of Group IV elements such asSiF₄, GeF₄, and fluorosilanes (e.g., SiFH₃, fluorotriethoxysilane,fluorodichloroethoxysilane), fluorogermanes (e.g., GeFH₃,fluorotriethoxygermane); fluorides of group V elements such as NF₃, PF₃,PF₅, PF₃Cl₂; fluorides of Group VI elements such as SF₄, SF₆, as well asfluoride salts such as NH₄HF₂, or mixed complexes thereof, or mixturesthereof. A preferred hydrofluoric acid source is a fluorosilane such asfluorotriethoxysilane. Thus, in certain embodiments, the sol gelprecursor can also function to provide some or the entire amount of thematrix dissolving agent.

Step (a) and (b) can be performed at a temperature between the solutionfreezing point and boiling point, typically between a temperature offrom about 0° C. to about 60° C. Step (b) can be performed such that thesolution forms a gel in situ or the solution or a portion of thesolution can be transferred to a receptacle and allowed to form a gel inthe receptacle. Any shape or form of receptacle is suitable, withoutlimitation. For example, the receptacle can be a capillary tubing (e.g.,comprising fused silica, borosilicate glass, doped silicate or glass), amold, a column, a chip, a microfluidics platform, a plate, or anintegrated analytical and detection system, e.g., including massspectrometric detection. Suitable sizes for capillary tubing includediameters of between about 10 μm and about 1000 μm, or more typicallybetween about 100 μm and about 530 μm.

Step (c) can be performed at a temperature up to about 400° C. Inpreferred methods, the temperature is from about 100° to about 200° C.,and in other preferred methods, the temperature is from about 200° toabout 400° C.

The method for preparing an ultraporous sol gel monolith can furthercomprise step (d) calcining the gel at a temperature of at least 400° C.Preferably, the gel is calcined at a temperature of from about 400° C.up to about 1000° C. or greater. In particular embodiments, the dryingand calcining steps are performed at the same time, by, for example,heating the sol gel to dryness at 200° C. and then increasing thetemperature to 400° C. or more. In addition, the drying and calciningsteps can be performed together by gradually raising the temperaturefrom below about 400° C. to a higher temperature in the range of 400° C.to about 1000° C. or greater. Further, the ultraporous sol gel monolithcan be solidified into a porous glass monolith, which is also useful forchromatographic separation or other purposes, and can be treated tomodify its pore surfaces, for example, using polymeric, organic orinorganic phases and/or layers that can be bonded and/or coated ontoporous glass monolith pore surfaces.

Organic materials, such as polymers or surfactants used as porogens, canbe removed from the porous sol gel by washing or exchanging externalsolvent prior to drying. However, washing is not a necessary step, andthe sol gel can be heated to a temperature high enough to vaporize orthermally decompose any organic porogen in order to remove it. Inaddition, heating the sol gel monolith provides greater strength.Preferably the sol gel monolith is heated to a temperature sufficient tocalcine the polysiloxane structure.

After the sol gel monolith is prepared and optionally calcined, the solgel monolith can be modified to produce bonded phases, e.g., by bondingdesirable chemical groups to provide particular adsorptioncharacteristics. The sol gel can also be endcapped, for example, using asmall silylating agent, such as trimethylchlorosilane, to react withresidual silanol groups present on the surface. These modifications arediscussed in greater detail below.

III. Sol gel precursors

Sol gel precursors include metal and metalloid compounds havinghydrolyzable ligands that can undergo a sol gel reaction and form solgels. Suitable hydrolyzable ligands include hydroxyl, alkoxy, halo,amino, or acylamino. The most common metal oxide participating in thesol gel reaction is silica, though other metals and metalloids are alsouseful, such as zirconia, vanadia, titania, niobium oxide, tantalumoxide, tungsten oxide, tin oxide, hafnium oxide and alumina, or mixturesor composites thereof, having reactive metal oxides, halides, amines,etc., capable of reacting to form a sol gel. Additional metal atoms canbe incorporated into the sol gel precursors include magnesium,molybdenum, cobalt, nickel, gallium, beryllium, yttrium, lanthanum, tin,lead, and boron, without limitation.

Preferred metal oxides and alkoxides include, but are not limited to,silicon alkoxides, such as tetramethylorthosilane (TMOS),tetraethylorthosilane (TEOS), fluoroalkoxysilane, or chloroalkoxysilane,germanium alkoxides (such as tetraethylorthogermanium (TEOG)), vanadiumalkoxides, aluminum alkoxides, zirconium alkoxides, and titaniumalkoxides. Similarly, metal halides, amines, and acyloxy derivatives canalso be used in the sol gel reaction.

In preferred embodiments, the sol gel precursor is an alkoxide ofsilicon, germanium, aluminum, titanium, zirconium, vanadium, or hafnium,or mixtures thereof. In particularly preferred embodiments, the sol gelprecursor is a silane. In a more preferred embodiment, the sol gelprecursor is a silane such as TEOS or TMOS.

In particular embodiments, the sol gel precursor can further include anorganic substituent. Sol gel precursors comprising an organicsubstituent include, without limitation, organosilanes having saturatedor unsaturated hydrocarbyl substituents, such as analkyltrialkoxysilane, cycloalkyltrialkoxysilane, dialkyldialkoxysilane,trialkylalkoxysilane, tetraalkoxysilane, vinyltrialkoxysilane,allyltrialkoxysilane, aryl substituents, such asphenylalkyldialkoxysilane, diphenylalkoxysilane, ornaphthyltrialkoxysilane, or mixtures thereof. The sol gel precursorcomprising an organic substituent can also include other organometalliccompounds such as organogermanes, or organosubstituted titanium,aluminum, zirconium or vanadium alkoxides, and the like. Suitablehydrocarbyl substituents can be C₁₋₁₀₀ or more typically C₁₋₃₀. Inanother preferred embodiment, the silane is a mixture of silanescomprising a trialkoxysilane and a tetraalkoxysilane.

IV. Porogens

The use of porogens aids in the preparation of the ultraporous sol gelmonolith. Preparation of the sol gel monolith in the presence of thephase separated volumes provides a sol gel monolith possessingmacropores and/or large mesopores, which provide greater porosity to thesol gel monolith, providing superior flow rates for solvent.

In one embodiment, the porogen can be a hydrophilic polymer. The amountand hydrophilicity of the hydrophilic polymer in the sol gel formingsolution affects the pore volume and size of macropores formed, andgenerally, no particular molecular weight range is required, although amolecular weight between about 1,000 to about 1,000,000 g/mole ispreferred. The porogen can be selected from, for example, polyethyleneglycol (PEG), sodium polystyrene sulfonate, polyacrylate,polyallylamine, polyethyleneimine, polyethylene oxide,polyvinylpyrrolidone, poly(acrylic acid), and can also include polymersof amino acids, and polysaccharides such as cellulose ethers or esters,such as cellulose acetate, or the like. Preferably, the polymer is a PEGhaving a molecular weight up to about 1,000,000 g/mole.

The porogen can also be an amide solvent, such as formamide, or an amidepolymer, such as poly(acrylamide), or a surfactant, such as a nonionicsurfactant, an ionic surfactant, an amphiphilic surfactant, or mixturesthereof. A preferred surfactant is the nonionic surfactant Pluronic F68(also known as Poloxamer).

Exemplary surfactants are those having an HLB value of between about10-25, such as polyethylene glycol 400 monostearate,polyoxyethylene-4-sorbitan monolaurate, polyoxyethylene-20-sorbitanmonooleate, polyoxyethylene-20-sorbitan monopalmitate,polyoxyethylene-20-monolaurate, polyoxyethylene-40-stearate, sodiumoleate and the like.

Nonionic surfactants are preferred in certain embodiments and include,for example, polyoxyl stearates such as polyoxyl 40 stearate, polyoxyl50 stearate, polyoxyl 100 stearate, polyoxyl 12 distearate, polyoxyl 32distearate, and polyoxyl 150 distearate, and other Myrj™ series ofsurfactants, or mixtures thereof. Yet another class of surfactant usefulas porogens are the triblock co-polymers of ethylene oxide/propyleneoxide/ethylene oxide, also known as poloxamers, having the generalformula HO(C₂H₄O)_(a)(—C₃H₆O)_(b)(C₂H₄O)_(a)H, available under thetradenames Pluronic and Poloxamer. Other useful surfactants includesugar ester surfactants, sorbitan fatty acid esters such as sorbitanmonolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitantristearate, and other Span™ series surfactants, glycerol fatty acidesters such as glycerol monostearate, polyoxyethylene derivatives suchas polyoxyethylene ethers of high molecular weight aliphatic alcohols(e.g., Brij 30, 35, 58, 78 and 99) polyoxyethylene stearate (selfemulsifying), polyoxyethylene 40 sorbitol lanolin derivative,polyoxyethylene 75 sorbitol lanolin derivative, polyoxyethylene 6sorbitol beeswax derivative, polyoxyethylene 20 sorbitol beeswaxderivative, polyoxyethylene 20 sorbitol lanolin derivative,polyoxyethylene 50 sorbitol lanolin derivative, polyoxyethylene 23lauryl ether, polyoxyethylene 2 cetyl ether with butylatedhydroxyanisole, polyoxyethylene 10 cetyl ether, polyoxyethylene 20 cetylether, polyoxyethylene 2 stearyl ether, polyoxyethylene 10 stearylether, polyoxyethylene 20 stearyl ether, polyoxyethylene 21 stearylether, polyoxyethylene 20 oleyl ether, polyoxyethylene 40 stearate,polyoxyethylene 50 stearate, polyoxyethylene 100 stearate,polyoxyethylene derivatives of fatty acid esters of sorbitan such aspolyoxyethylene 4 sorbitan monostearate, polyoxyethylene 20 sorbitantristearate, and other Tween™ series of surfactants, phospholipids andphospholipid fatty acid derivatives such as lecithins, fatty amineoxides, fatty acid alkanolamides, propylene glycol monoesters andmonoglycerides, such as hydrogenated palm oil monoglyceride,hydrogenated soybean oil monoglyceride, hydrogenated palm stearinemonoglyceride, hydrogenated vegetable monoglyceride, hydrogenatedcottonseed oil monoglyceride, refined palm oil monoglyceride, partiallyhydrogenated soybean oil monoglyceride, cotton seed oil monoglyceridesunflower oil monoglyceride, sunflower oil monoglyceride, canola oilmonoglyceride, succinylated monoglycerides, acetylated monoglyceride,acetylated hydrogenated vegetable oil monoglyceride, acetylatedhydrogenated coconut oil monoglyceride, acetylated hydrogenated soybeanoil monoglyceride, glycerol monostearate, monoglycerides withhydrogenated soybean oil, monoglycerides with hydrogenated palm oil,succinylated monoglycerides and monoglycerides, monoglycerides andrapeseed oil, monoglycerides and cottonseed oils, monoglycerides withpropylene glycol monoester sodium stearoyl lactylate silicon dioxide,diglycerides, triglycerides, polyoxyethylene steroidal esters, Triton-Xseries of surfactants produced from octylphenol polymerized withethylene oxide, where the number “100” in the trade name is indirectlyrelated to the number of ethylene oxide units in the structure, (e.g.,Triton X-100™ has an average of N=9.5 ethylene oxide units per molecule,with an average molecular weight of 625) and having lower and highermole adducts present in lesser amounts in commercial products, as wellas compounds having a similar structure to Triton X-100™, includingIgepal CA-630™ and Nonidet P-40M (NP-40™, N-lauroylsarcosine, SigmaChemical Co., St. Louis, Mo.), and the like. Any hydrocarbon chains inthe surfactant molecules can be saturated or unsaturated, hydrogenatedor unhydrogenated.

An especially preferred family of surfactants are the poloxamersurfactants, which are a:b:a triblock co-polymers of ethyleneoxide:propylene oxide:ethylene oxide. The “a” and “b” represent theaverage number of monomer units for each block of the polymer chain.These surfactants are commercially available from BASF Corporation ofMount Olive, N.J., in a variety of different molecular weights and withdifferent values of “a” and “b” blocks. For example, Lutrol® F127 has amolecular weight range of 9,840 to 14,600 and where “a” is approximately101 and “b” is approximately 56, Lutrol F87 represents a molecularweight of 6,840 to 8,830 where “a” is 64 and “b” is 37, Lutrol F108represents an average molecular weight of 12,700 to 17,400 where “a” is141 and “b” is 44, and Lutrol F68 represents an average molecular weightof 7,680 to 9,510 where “a” has a value of about 80 and “b” has a valueof about 27.

Sugar ester surfactants include sugar fatty acid monoesters, sugar fattyacid diesters, triesters, tetraesters, or mixtures thereof, althoughmono- and di-esters are most preferred. Preferably, the sugar fatty acidmonoester comprises a fatty acid having from 6 to 24 carbon atoms, whichmay be linear or branched, or saturated or unsaturated C₆ to C₂₄ fattyacids. The C₆ to C₂₄ fatty acids are preferably chosen from stearates,behenates, cocoates, arachidonates, palmitates, myristates, laurates,carprates, oleates, laurates and their mixtures, and can include even orodd numbers of carbons in any subrange or combination. Preferably, thesugar fatty acid monoester comprises at least one saccharide unit, suchas sucrose, maltose, glucose, fructose, mannose, galactose, arabinose,xylose, lactose, sorbitol, trehalose or methylglucose. Disaccharideesters such as sucrose esters are most preferable, and include sucrosecocoate, sucrose monooctanoate, sucrose monodecanoate, sucrose mono- ordilaurate, sucrose monomyristate, sucrose mono- or dipalmitate, sucrosemono- and distearate, sucrose mono-, di- or trioleate, sucrose mono- ordilinoleate, sucrose polyesters, such as sucrose pentaoleate,hexaoleate, heptaoleate or octooleate, and mixed esters, such as sucrosepalmitate/stearate.

Particularly preferred examples of these sugar ester surfactants includethose sold by the company Croda Inc of Parsippany, N.J. under the namesCrodesta F10, F50, F160, and F110 denoting various mono-, di- andmono/di ester mixtures comprising sucrose stearates, manufactured usinga method that controls the degree of esterification, such as describedin U.S. Pat. No. 3,480,616.

Use may also be made of those sold by the company Mitsubishi under thename Ryoto Sugar esters, for example under the reference B370corresponding to sucrose behenate formed of 20% monoester and 80% di-,tri- and polyester. Use may also be made of the sucrose mono- anddipalmitate/stearate sold by the company Goldschmidt under the name“Tegosoft PSE”. Use may also be made of a mixture of these variousproducts. The sugar ester can also be present in admixture with anothercompound not derived from sugar; and a preferred example includes themixture of sorbitan stearate and of sucrose cocoate sold under the name“Arlatone 2121” by the company ICI. Other sugar esters include, forexample, glucose trioleate, galactose di-, tri-, tetra- or pentaoleate,arabinose di-, tri- or tetralinoleate or xylose di-, tri- ortetralinoleate, or mixtures thereof. Other sugar esters of fatty acidsinclude esters of methylglucose include the distearate of methylglucoseand of polyglycerol-3 sold by the company Goldschmidt under the name ofTegocare 450. Glucose or maltose monoesters can also be included, suchas methyl O-hexadecanoyl-6-D-glucoside and O-hexadecanoyl-6-D-maltose.Certain other sugar ester surfactants include oxyethylenated esters offatty acid and of sugar include oxyethylenated derivatives such asPEG-20 methylglucose sesquistearate, sold under the name “GlucamateSSE20”, by the company Amerchol.

One of the characteristics of surfactants is the HLB value, orhydrophilic lipophilic balance value. This value represents the relativehydroplicility and relative hydrophobicity of a surfactant molecule.Generally, the higher the HLB value, the greater the hydrophilicity ofthe surfactant while the lower the HLB value, the greater thehydrophobicity. For the Lutrol® molecules, for example, the ethyleneoxide fraction represents the hydrophilic moiety and the propylene oxidefraction represents the hydrophobic fraction. The HLB values of LutrolF127, F87, F108, and F68 are respectively 22.0, 24.0, 27.0, and 29.0.The preferred sugar ester surfactants provide HLB values in the range ofabout 3 to about 15.

V. Bonded Phases

After preparation of the ultraporous sol gel monolith, the sol gel canbe modified with a bonded phase if desired. Bonded phases can beprepared using conventional techniques known in the art, or as practicedin co-pending U.S. Ser. No. 10/777,523 filed Feb. 12, 2004, adapted ifnecessary for modifying a monolithic form (e.g., flowing reactantsthrough the monolith). Bonded phases can include hydrocarbyl moieties,such as C₁₋₁₀₀, or more typically C₁₋₃₀ (e.g., C₁₈ or C₈), aryl moieties(e.g., phenyl or naphthyl), or polar moieties such as cyano, urethane,carbamido, amino, sulfonamide, (e.g., cyanopropyl,C₁₅H₃₁CONH(CH₂)₃Si(OMe)₃, CH₃CONH(CH₂)₃Si(OMe)₃),C₈H₁₇OCONH(CH₂)₃Si(OEt)₃, NC(CH₂)₃SiMe₂Cl, and the like, withoutlimitation. The silanes used in the preparation of bonded phases areavailable commercially or can be prepared by conventional syntheticmethods. Silanes having polar moieties can be utilized to provide abonded phase having polar moieties bonded thereto. Polar silanes can besynthesized by one skilled in the art of organic synthesis, for example,by reaction of the appropriate allyl ether, amide, carbamide, etc., withdimethylethoxysilane to yield the dimethylethoxysilane having thedesired polar component. For example,O-alkyl-N-(trialkoxysilylalkyl)urethanes can be prepared as described inU.S. Pat. No. 6,071,410 to Nau et al. Additional polar silanes aredescribed in U.S. Pat. Nos. 6,645,378 to Liu et al. and 5,374,755 toNeue et al.

In particular embodiments, the silane has the formula

R¹ _(n)—Si—X_(4-n),

wherein R¹ is independently selected from hydrogen, C₁-C₁₀₀ substitutedor unsubstituted hydrocarbyl, cycloalkyl, heterocycloalkyl, aryl, orheteroaryl; wherein the substituents are selected from C₁-C₁₂hydrocarbyl, hydroxyl, alkoxy, halogen, amino, nitro, sulfo, cyano,glycidyl, carbamido, and carbonyl, wherein n is 0, 1, 2, or 3, wherein Xis a leaving group. X can be a halogen, C₁-C₁₂ alkoxy, amino, or C₁-C₁₂acyloxy, and when X is halogen, n is not 0.

Bonded phases can also include phases generated by endcapping.Endcapping is desirable in some embodiments, as it may decreaseundesirable adsorption of basic or ionic compounds or provide particulardesirable adsorption properties. Appropriate end capping reagentsinclude short-chain silanes such as trimethylchlorosilane,trimethylsilylimidazole (TMSIM),bis-N,O-trimethylsilyltrifluoroacetamide (BSTFA),bis-N,O-trimethylsilylacetamide (BSA), trimethylsilyldimethylamine(TMSDMA), trimethylchlorosilane (TMS), and hexamethyldisilane (HMDS),and the like, without limitation. Preferred end-capping reagents includetrimethylchlorosilane (TMS), trimethylchlorosilane (TMS) with pyridine,and trimethylsilylimidazole (TMSIM).

VI. Characterization of the Ultraporous Sol Gel Monoliths

The pore size distribution curve is determined from the derivative ofthe pore volume (V) with respect to the pore diameter (D) (dV/d log D),plotted against the pore diameter (D). The mode pore size is the poresize for which the value of dV/d log D of the pore size distributioncurve is greatest (the maximum peak exhibited). This pore sizedistribution curve is derived from the adsorption isotherm obtained bymeasurement of the adsorption of nitrogen gas, for example, according toseveral equations. The adsorption isotherm measurement method generallyinvolves cooling the sample to liquid nitrogen temperature, introducingnitrogen gas, and determining the amount of nitrogen adsorbed by fixeddisplacement or gravimetry. The pressure of the introduced nitrogen gasis gradually increased, and the adsorption of nitrogen gas at eachequilibrium pressure is plotted to produce an adsorption isotherm. Thepore size distribution curve can be derived from this adsorptionisotherm according to the equation for the Cranston-Inklay method,Dollimore-Heal method, BET method, BJH method, and so forth.

As described herein, the total surface area and micropore volume can beconveniently determined using an instrument such as the MicromeriticsTriStar 3000. The total surface area is preferably calculated using theBET method, and the micropore volume is calculated using the t-plotmethod, as described in by Mikail, R., et al. (1968) J. ColloidInterface Sci. 26:45. The t-plot method can be used to detect thepresence of the micropores in the sample, and to determine their volume.The t-plot is a curve of the nitrogen adsorption (v/g) plotted againstthe mean film thickness (t) of the adsorption film (where the x-axis isthe mean film thickness and the y-axis is the adsorption). The amount ofnitrogen adsorbed versus thickness of the layer is linear if nomicropores or mesopores exist. Conversely, the presence of microporescan be detected by the loss of nitrogen adsorption at a particularthickness, and the diameter of the pore that no longer providesaccessible surface areas can be calculated.

In FIGS. 2 and 3, t-plots are shown that correspond to the experimentaldata obtained and presented in Examples 2 and 4. The intercept of thet-plot goes through zero, indicating that the micropore volume isvirtually zero. The preparation of ultraporous sol gel monolith withsubstantially no micropores is a surprising and significant advance inthe art.

Mesopore distribution curves are shown in FIGS. 4 and 5. These plotsdemonstrate that the ultraporous sol gel monolith produced by theprocedures set forth in Examples 1 and 2, respectively, have narrow poresize distributions centered at mesopore mode diameter of about 102 Å and160 Å.

VII. Advantages of the Ultraporous Sol Gel Monolith

The methods for preparing the ultraporous sol gel monoliths are simple,cost effective and time saving. In contrast, the prior art methodsrequire preparation of the sol gel and subsequent thermal or chemicalreorganization treatments to modify the structure to generate or modifythe mesopore distribution in the sol gel. These methods also generallyfail to eliminate micropores that interfere with separations.

The ultraporous sol gel monoliths of the invention provide superiorsorbents for chromatography as well as other analytical separations orsample preparation procedures. Micropores are virtually eliminated fromthe sol gel monolith prepared using the methods of the invention,providing a sorbent having predictable and controllable solvent andsolute accessible volumes.

The monolithic structure is ultraporous, allowing low operatingpressures, well below those routinely used in conventional HPLCseparations. As shown in Example 8, the mobile phase pressures that wereused with the ultraporous sol gel monolith are significantly lower thanutilized in conventional HPLC. Alternatively, the ultraporous structureallows flow rates up to 10 times faster than used in conventional HPLC.Accordingly, the ultraporous sol gel monolithic structure allowsincreased separation speeds, and consequently, faster separations, whichis a major advance in separation efficiency as well as laboratoryanalysis time and labor.

Sol gels can be formed directly in a capillary column or otherreceptacle, and pretreatment or etching of the capillary is optional forall applications due to the high concentration of matrix dissolvingcatalyst in the solution. No frit is required to contain the sol gel,and no packing of columns is required, which is a time and laborintensive step.

The sol gel monoliths can be conveniently adapted to microfluidicsapplications and devices, and could be used advantageously in massspectrometric or other analytical procedures where higher sensitivity isadvantageously coupled with smaller analytical sorbent volumes at thesame or faster solvent flow rates.

VIII. Applications

The ultraporous sol gel monoliths produced by the methods of thisinvention can be advantageously used in chromatographic and analyticalseparations applications in the form of chromatographic columns or otherdevices, where such devices have improved flow properties, reduced backpressure, reduced micropores and reduced silanol residues, whicheliminate peak tailing for basic analytes. For example, the sol gelmonolith can be incorporated into capillary column, or a cartridgesystem. Since monolithic sorbents are rigid and dead space may ariseduring the cladding, the cladding of the monoliths to provide columns,filters, or cartridges or the like having no dead space and in apressure-stable manner can be challenging. In one embodiment, the solgel monolith can be used to prepare a cartridge, for example, asdescribed in U.S. Pat. No. 6,797,174, which describes a clad column witha monolithic sorbent on which a cap is installed at least at one end,and a connecting system consisting of at least one divided supportingscrew and at least one end piece which is screwed onto the supportingscrew for the connection of eluent feed and discharge. Alternatively, asdescribed in Example 8, the sol gel monolith can be incorporated into acartridge system without the use of a cap.

In a particularly advantageous embodiment, the chromatographic device isa chromatographic column, such as an HPLC column, as described inExample 8. FIG. 1B shows a scanning electron micrograph of across-section of an ultraporous sol gel monolith formed in capillarytubing having an internal diameter of 530 μm. The ultraporous monolithicstructure can be seen, and can be advantageously applied to HPLCseparations with improved flow properties.

The ultraporous sol gel monoliths can also be used in planar form forplanar applications (e.g., thin layer applications), such as TLC platesor as a component of a microfluidics device utilizing planar separation,as well as other planar geometries such as filtration devices andmembranes, solid phase extraction media, or microtiter plates. Any shapecan be formed, without limitation, such as rod shaped, spheres, hollowor filled structures (e.g., hollow tubes), flat sheets, fibers, chips,micro- or nano-sized wires or other shapes useful in microfluidicsapplications.

The ultraporous sol gel monoliths can also be solidified into a porousglass monolith by subjecting the monolith to high temperaturecalcination, and is also useful in this form for chromatographicseparation or other purposes by modifying its pore surfaces. Forexample, polymeric, organic or inorganic phases and/or layers can bebonded and/or coated onto porous glass monolith pore surfaces to provideparticular adsorption properties.

The ultraporous sol gel monoliths can also be used in otherapplications, such as filtration, solid phase synthesis, bioreactors,catalysis, resins, sensor devices, medical devices and drug or otheractive agent delivery platforms, and the like. The methods are alsoapplicable to the preparation of devices for carrying out suchapplications. The ultraporous sol gel monoliths can include inorganic aswell as organic or biological components. The ultraporous sol gelmonoliths can be used as a stationary phase that includes ultraporousinorganic/organic and/or biological hybrid materials. The stationaryphase may be introduced by polymerization in situ or by packing,inserting, coating, impregnating, cladding, wrapping, or otherart-recognized techniques, etc., depending on the requirements of theparticular device. In a preferred embodiment, the ultraporous sol gelmonolith is formed in situ in such devices. In another preferredembodiment, the ultraporous sol gel monolith is formed in a mold andtransferred to the site of intended use.

In a preferred embodiment, a method of separating a mixture of analytesis provided, comprising applying the mixture of analytes to theultraporous sol gel monolith, and eluting the analytes using a mobilephase. Suitable separations can be performed using thin layerchromatography, high performance liquid chromatography, reversed phasechromatography, normal phase chromatography, ion chromatography, ionpair chromatography, reverse phase ion pair chromatography, ion exchangechromatography, affinity chromatography, hydrophobic interactionchromatography, size exclusion chromatography, chiral recognitionchromatography, perfusion chromatography, electrochromatography,partition chromatography, microcolumn liquid chromatography, capillarychromatography, capillary zone electrophoresis (CZE), nano-LC, opentubular liquid chromatography (OTLC), capillary electrochromatography(CEC), liquid-solid chromatography, preparative chromatography,hydrophilic interaction chromatography, supercritical fluidchromatography, precipitation liquid chromatography, bonded phasechromatography, fast liquid chromatography, flash chromatography, liquidchromatography-mass spectrometry, gas chromatography, microfluidicsbased separations, chip based separations or solid phase extractionseparations.

In particular embodiments, the ultraporous sol gel monoliths of theinvention can be used in a method of preparing devices for capillary andmicrofluidics applications, which typically utilize small columninternal diameters (<100 micron i.d.) and low mobile phase flow rates(<300 mL/min). Techniques such as capillary chromatography, capillaryzone electrophoresis (CZE), nano-LC, open tubular liquid chromatography(OTLC), and capillary electrochromatography (CEC) offer numerousadvantages over conventional scale high performance liquidchromatography (HPLC). These advantages include higher separationefficiencies, high-speed separations, analysis of low volume samples,and the coupling of 2-dimensional techniques. However, even theseapplications can benefit from the ultraporous sol gel monolithsdescribed herein, which provides the possibility of even higher flowrates and more uniform and controllable pore size distributions.

Microchip-based separation devices have been developed for rapid sampleanalysis. Examples of microchip-based separation devices include thosefor capillary electrophoresis, capillary electrochromatography andhigh-performance liquid chromatography. For example, the sol gelmonolith can be incorporated into a chromatographic chip, which can bemade, for example, by forming grooves on a plate and forming a silicagel having a monolithic bimodal pore structure in the grooves. Arepresentative chromatographic chip and method for preparing and usingit is described in U.S. Patent Application Publication No. 20030230524to Naohiro. These and other separation devices are capable of fastanalyses and provide improved precision and reliability compared toother conventional analytical instruments. Compared to otherconventional separation devices, these microchip-based separationdevices have higher sample throughput, reduced sample and reagentconsumption, and reduced chemical waste. The liquid flow rates formicrochip-based separation devices range from approximately 1-300nanoliters per minute for most applications. The ultraporous sol gelmonoliths described herein can be incorporated into these microfluidicsdesigns, providing a monolithic sorbent within microchannels onmicrochip-based separation device, thereby providing greater flow ratesfor microchip applications as well.

It is to be understood that while the invention has been described inconjunction with the preferred specific embodiments thereof, that thedescription above as well as the examples that follow are intended toillustrate and not limit the scope of the invention. The practice of thepresent invention will employ, unless otherwise indicated, conventionaltechniques of organic chemistry, polymer chemistry, biochemistry and thelike, which are within the skill of the art. Other aspects, advantagesand modifications within the scope of the invention will be apparent tothose skilled in the art to which the invention pertains. Suchtechniques are explained fully in the literature.

In the following examples, efforts have been made to ensure accuracywith respect to numbers used (e.g., amounts, temperature, etc.) but someexperimental error and deviation should be accounted for. Unlessindicated otherwise, temperature is in degrees ° C. and pressure is ator near atmospheric. All solvents were purchased as HPLC grade, and allreactions were routinely conducted in the air unless otherwiseindicated. Unless otherwise indicated, the reagents used were obtainedfrom the following sources: PEG and TEOS were obtained from Alfa Aesar,surfactants from BASF, and HF from Fisher Scientific.

ABBREVIATIONS

-   TEOS tetraethoxysilane-   PEG polyethylene glycol-   HF hydrofluoric acid

EXAMPLE 1 Formation of a Sol Gel Monolith without Micropores

Preparation of the Sol Gel:

Polyethylene glycol (PEG) (1.1 g, MW 20,000) was dissolved in themixture of 2.5 g hydrofluoric acid (HF, 1.2 M) and 4.3 g methanol. Whilestirring, tetraethoxysilane (TEOS, 5.6 g) was introduced into thesolution and formed a uniform mixture. Five minutes later, the mixturewas cast into test tubes and kept at 5° C. The sols became white gelsafter half an hour, which were then dried and calcined for 10 hours at atemperature of 600° C. FIG. 1A shows a scanning electron microscopic(SEM) image (×3000) of the gel structure. The SEM photomicrographconfirms that the sol gel has an ultraporous monolithic structure.

Characterization of the Sol Gel:

Using a Micromeritics TriStar 3000 (Norcross, Ga.), the BET surface areawas determined to be 531 m²/g, mesopore volume was 1.13 cc/g andmesopore mode diameter was 102 Å, as shown in FIG. 4. t-Plot analysisindicated virtually no micropores. The total pore volume of 5.4 cc/g wasdetermined using mercury intrusion (Mercury Porosimeter, PorousMaterials Incorp., Ithaca, N.Y.). This measurement technique indicatesthe presence of macropores having a diameter of about 1.3 μm.

This experiment demonstrates that the method for forming the ultraporoussol gel monolith produces a highly porous structure (total porosity>90%)containing macropores having pore diameters of about 1.3 μm, andmesopores having a pore diameter of about 100 Å. The mesopore volume wasabout 21% of the total pore volume. Virtually no micropores wereobserved.

EXAMPLE 2 Formation of an Inorganic Sol Gel Monolith

In a similar experimental design to that described in Example 1, PEG(1.06 g, MW 10,000) was dissolved in a solution mixture of methanol(4.31 g), water (1.33 g) and hydrofluoric acid (HF, 1.16 g, 2.6 M).While stirring, TEOS (5.60 g) was introduced into the mixture and formeda uniform solution. After 5 minutes, the sol was cast into test tubesand kept at 5° C. About 30 minutes later, all sols became white gels,which were dried and calcined at 600° C. The total pore volume wasmeasured to be 4.6 cc/g using a mercury intrusion test. Nitrogenabsorption was done on Micromeritics TriStar 3000, BET surface area was290 m²/g, the mesopore mode diameter was 162 Å, as shown in FIG. 5, andthe mesopore volume was 1.50 cc/g (P/P₀=0.98). Virtually no microporeswere detected using t-plot, as shown in FIG. 2

EXAMPLE 3 Formation of an Inorganic Sol Gel Monolith

PEG (0.71 g, MW 20,000) was dissolved in a solution mixture of methanol(2.87 g), ethanol (1.65 g), water (0.88 g) and hydrofluoric acid (HF,0.77 g, 2.6 M). While stirring, tetraethoxysilane (TEOS, 3.74 g) wasintroduced into the mixture and formed a uniform solution. After 5minutes, the sol was cast into test tubes and kept at 25° C. About 40minutes later, all sols became white gels, which were dried and calcinedat 600° C. The total pore volume was measured to be 5.0 cc/g using amercury intrusion test. Nitrogen absorption was performed using aMicromeritics TriStar 3000, and the BET surface area 452 m²/g, themesopore mode diameter was 142 Å, and the mesopore volume was 1.34 cc/g(P/P₀=0.98). Virtually no micropores were detected using t-plot.

EXAMPLE 4 Formation of an Inorganic Sol Gel Monolith without Micropores

The nonionic surfactant Pluronic F68 (0.44 g, BASF) was dissolved in amixture of 1.11 g water, 3.59 g methanol, 2.07 g reagent alcohol and0.96 g HF (2.6 M). While stirring, 5.0 ml TEOS (4.67 g) was introducedinto the above solution and formed a uniform mixture. After 5 minutes,the sol was cast into test tubes and kept at room temperature. After 30minutes, all sols became white gels, which were then dried and calcinedfor 10 hours at a temperature of 600° C.

BET surface area, mesopore volume and mode diameter measurements wereperformed using a Micromeritics TriStar 3000: the BET surface area was526 m²/g, the mesopore volume was 1.46 cc/g, and the mesopore modediameter was 136 Å. Virtually no micropores were detected using t-plotanalysis, as shown in FIG. 3. The total pore volume was determined asabout 6.9 cc/g using a mercury intrusion test. The mesopore volume wasabout 21% of the total pore volume.

EXAMPLE 5 Formation of an Inorganic Sol Gel Monolith without Micropores

The nonionic surfactant Pluronic F68 (0.88 g, BASF) was dissolved in amixture of 1.11 g water, 3.59 g methanol, 2.07 g reagent alcohol and0.96 g HF (2.6 M). While stirring, 5.0 ml TEOS (4.67 g) was introducedinto the above solution and formed a uniform mixture. After 5 minutes,the sol was cast into test tubes and kept at 5° C. After about one hour,all sols became white gels, which were dried and calcined for 10 hoursat a temperature of 600° C.

BET surface area, mesopore volume and mode diameter measurements wereperformed using a Micromeritics TriStar 3000. The BET surface area was550 m²/g, the mesopore volume was 1.36 cc/g, and the mesopore diameterwas 108 Å. The total pore volume was determined as about 6.2 cc/g usinga mercury intrusion test. Virtually no micropores were detected usingt-plot analysis. The mesopore volume was about 22% of the total porevolume.

EXAMPLE 6 Formation of a Hybrid Organic/Inorganic Sol Gel Monolithwithout Micropores

In a similar experimental design to that described in Example 1, thenonionic surfactant Pluronic F68 (0.47 g, MW 8,400) was dissolved in asolution mixture of methanol (3.78 g), reagent alcohol (2.17 g) andhydrofluoric acid (HF, 2.62 g, 1.2 M). While stirring, a mixture oftetraethoxysilane (TEOS, 4.67 g) and methyl triethoxysilane (0.22 g) wasintroduced into the solution and formed a uniform solution. After 5minutes, the sol was cast into test tubes and kept at 5° C. The solsbecame white gels within 30-40 minutes, and were dried at 180° C.

The total pore volume was estimated to be above 5.6 cc/g and porositywas above 90%. Using a Micromeritics TriStar 3000, the BET surface areameasurement was 614 m²/g, the mesopore volume was 1.25 cc/g and themesopore mode diameter was 104 Å. The mesopore volume was about 22% ofthe total pore volume. Virtually no micropores were detected usingt-plot.

This experiment demonstrates that the use of the combination of organicand inorganic silanes results in a sol gel with a porosity of greaterthan 90%. As before, virtually no micropores were observed.

EXAMPLE 7 Formation of a Hybrid Organic/Inorganic Sol Gel Monolithwithout Micropores

The nonionic surfactant Pluronic F68 (0.47 g, MW 8,400) was dissolved ina solution mixture of methanol (3.78 g), reagent alcohol (2.17 g) andhydrofluoric acid (HF, 3.06 g, 1.2 M). While stirring, a mixture oftetraethoxysilane (TEOS, 4.67 g) and octyl triethoxysilane (0.34 g) wasintroduced into the solution and formed a uniform solution. After 5minutes, the sol was cast into test tubes and kept at 25° C. Fifteen totwenty minutes later, all sols became white gels, which were dried at180° C.

Total pore volume was estimated to be about 5.2 cc/g and porosity wasabove 90%. A multi-point BET surface area measurement of 663 m²/g wasobtained using a Micromeritics TriStar 3000, the mesopore volume was1.11 cc/g and the mesopore mode diameter was about 85 Å. Virtually nomicropores were detected using t-plot. The mesopore volume was about 21%of the total pore volume.

This experiment demonstrates that the use of the combination of organicand inorganic silanes results in a sol gel with a porosity of greaterthan 90%. The surface area appears to be increased relative to the solgel produced using only TEOS. As before, virtually no micropores wereobserved.

EXAMPLE 8 Comparison of a Chromatography Column Prepared Using anInorganic Sol Gel Monolith with a Conventional HPLC ChromatographyColumn Prepared Using Silica Beads

A chromatography column was prepared using a glass-lined stainless steeltubing (GLT) having an internal diameter of 0.3 mm and 150 mm in length.A solution was prepared as described in Example 1, and injected into theGLT tubing without etching or pretreatments and kept at 5° C. overnight.The column was then dried and calcined for 10 hours at a temperature of600° C.

The column characteristics were tested by measuring the pressurerequired to run solvent through the column. The column flows at a flowrate of above 30 microliter per minute operated at about 100 bars. Incontrast, a column of the same diameter and length packed withconventional 5 micron silica beads exhibited a flow rate of only about 4microliter per minute under the same conditions. The mobile phase ineach case was methanol/water 80:20.

A rod of dimensions 2.0 mm diameter and 50 mm length was also preparedas described in Example 1. Shrinkable Teflon tubing was used to protectthe rod and produce a column without any caps on the ends. This columnexhibited a flow rate of 200 μl/min with back pressure less than 100psi. In contrast, a conventional column with the same inner diameter andlength, packed with 5 micron particles, exhibited a flow rate of 200μl/min at above 500 psi. The mobile phase in each case wasmethanol/water 80:20.

These results demonstrate the superior flow characteristics provided bythe ultraporous sol gel monolith in comparison with a conventionalchromatographic sorbent.

1-19. (canceled)
 20. A method of separating a mixture of analytes,comprising applying the mixture of analytes to the ultraporous sol gelmonolith having a total porosity of up to about 97% with substantiallyno pores having diameters less than about 2.0 mm; and eluting theanalytes using a mobile phase.
 21. The method of claim 20, wherein themethod of separating is thin layer chromatography, high performanceliquid chromatography, reversed phase chromatography, normal phasechromatography, ion chromatography, ion pair chromatography, reversephase ion pair chromatography, ion exchange chromatography, affinitychromatography, hydrophobic interaction chromatography, size exclusionchromatography, chiral recognition chromatography, perfusionchromatography, electrochromatography, partition chromatography,microcolumn liquid chromatography, capillary chromatography, capillaryzone electrophoresis (CZE), nano-LC, open tubular liquid chromatography(OTLC), capillary electrochromatography (CEC), liquid-solidchromatography, preparative chromatography, hydrophilic interactionchromatography, supercritical fluid chromatography, precipitation liquidchromatography, bonded phase chromatography, fast liquid chromatography,flash chromatography, liquid chromatography-mass spectrometry, gaschromatography, microfluidics based separations, chip based separations,or solid phase extraction separations.